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The respiratory system is well defended against inhaled bacteria by a dynamic system of interacting layers, including mucociliary clearance, host defense factors including antimicrobial peptides in the epithelial lining fluid, proinflammatory responses of the respiratory epithelium, resident alveolar macrophages, and recruited neutrophils and monocytes. Nevertheless, these manifold defenses are susceptible to failure as a result of stress, glucocorticoids, viral infections, abrupt exposure to cold air, and poor air quality. When some of these defenses fail, the lung can be colonized by bacterial pathogens that are equipped to evade the remaining defenses, resulting in the development of pneumonia. This review considers the mechanisms by which these predisposing factors compromise the defenses of the lung, with a focus on the development of bacterial pneumonia in cattle and supplemented with advances based on mouse models and the study of human disease. Deepening our understanding of how the respiratory defenses fail is expected to lead to interventions that restore these dynamic immune responses and prevent disease.

Failure of Respiratory Defenses in the Pathogenesis of Bacterial Pneumonia of Cattle